PROJECT SUMMARY/ABSTRACT The long-term goals of the present study are to improve surgical outcomes and reduce the risk of surgical complications of cataract surgery. It is our central hypothesis that intraoperative stabilization of the ocular structures, complete lens extraction, and accurate positioning of the intraocular lens implant through robotic manipulations and optical coherence tomography (OCT) feedback will significantly improve the safety of critical surgical steps in cataract surgery. Through improvements in visualization and tool control, we theorize that the risk of secondary cataracts, posterior capsule rupture, ametropia, and other surgical complications can be eliminated to improve safety and abate the costs associated with cataract surgery and follow-up procedures. Our main objective is to develop the technology necessary to realize per-operative stabilization and imaging of ocular structures, complete lens extraction, and accurate positioning of the intraocular lens implant. Our group has developed the Intraocular Robotic Intervention and Surgical System (IRISS) to perform semi- automated cataract surgery on ex-vivo pig eyes [1?7] through a combination of internal funding and a recent R21 grant (NIH/R21EY024065). Through transpupillary OCT-guided automation, the IRISS has achieved notable success in semi-automated cataract extraction. There are three independent specific aims. First, to control the surgical environment and improve intraocular imaging quality, an integrated docking apparatus will constrain the eyeball motion and limit the motion of intraocular tissues through intraocular pressure control while allowing tool access for intraocular manipulations. Second, complete lens extraction will be enabled by an intraocular OCT imaging probe; precise feedback control of the tool mounted and driven by the IRISS; and the real-time visualization of the iris, cornea, and entire lens (including its posterior capsule and equator). Third, the ability to intraoperatively sense and control the intraocular lens six degrees-of-freedom position and orientation will be realized through a new custom tool guided by the transpupillary and intraocular OCT feedback. It is important to note that while the ultimate goal is the integration of all three aims into an automated system, their development remains independent and success or failure in one does not affect the outcome of another. The proposed contribution is significant because it offers to eliminate several common complications of cataract surgery including posterior capsule rupture, secondary cataracts, and ametropia. The proposed research is innovative because of its development of (1) a pressure-regulated docking device that stabilizes intraocular tissue while allowing the access of intraocular tool and improved quality of per-operative imaging, (2) visualization of the lens equator through an intraocular OCT probe and real-time image guided robotic instrument control for complete lens extraction and capsule cleaning, and (3) robotic control over the intraocular lens implantation and positioning of the intraocular lens.